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The Zika outbreak that began in 2015 has spread from Brazil to countries across the Western Hemisphere including the United States, presenting global public health challenges that call for the expedited development and availability of preventive vaccines to protect against Zika virus disease. While the general principles guiding the nonclinical and clinical development for Zika vaccines are the same as those of other preventive vaccines, unique considerations apply, in particular if development occurs during a public health emergency. Furthermore, incomplete information about the pathogenesis of Zika virus disease and the mechanism by which candidate preventive vaccines potentially may confer protection presents additional challenges to their clinical development. Nevertheless, definition of clinical development strategies to enable sound regulatory assessment, with a goal toward licensure is critical for these products. This article will provide an overview of the regulatory considerations for the clinical development and licensure of Zika vaccine candidates including a discussion of clinical study designs, approaches to demonstrate vaccine effectiveness, and regulatory pathways to licensure.

Routine use of the pneumococcal conjugate vaccines (PCV7 and PCV13), beginning in 2000, has resulted in a dramatic reduction in the incidence of invasive pneumococcal disease (IPD) attributable to serotypes of Streptococcus pneumoniae contained in the vaccines. The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention and the American Academy of Pediatrics recommend the expanded use of PCV13 in children 6 through 18 years of age with certain conditions that place them at elevated risk of IPD. This statement provides recommendations for the use of PCV13 in children 6 through 18 years. A single dose of PCV13 should be administered to certain children in this age group who are at elevated risk of IPD. Recommendations for the use of PCV13 in healthy children and for pneumococcal polysaccharide vaccine (PPSV23) remain unchanged.

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus. Chikungunya disease (CHIK) in humans is characterized by sudden onset of high fever, cutaneous rash, myalgia and debilitating polyarthralgia. Until recently the virus was considered endemic to only Africa and Asia, but since 2004 CHIK has spread to previously non-endemic regions, including Europe and the Americas, thereby emerging as a global health threat. Although a variety of CHIKV vaccine candidates have been tested in animals, and a few have advanced to human clinical trials, no licensed vaccine is currently available for prevention of disease. In this article, we review recent efforts in CHIKV vaccine development and discuss regulatory considerations for CHIKV vaccine licensure under U.S. FDA regulations. Several licensure pathways are available, and the most appropriate licensure pathway for a CHIK vaccine will depend on the type of evidence that can be generated to demonstrate the vaccine's effectiveness. If "traditional approval" following demonstration of direct benefit in adequate and well-controlled clinical disease endpoint studies is not possible, the Accelerated Approval and Animal Rule pathways are potential alternatives. In terms of vaccine safety, the potential for vaccine associated arthralgia and antibody-dependent enhancement of infectivity and disease severity are important issues that should be addressed in both pre-clinical and clinical studies. CHIK vaccine developers are encouraged to communicate with the FDA during all stages of vaccine development.

Palivizumab was licensed in June 1998 by the Food and Drug Administration for the reduction of serious lower respiratory tract infection caused by respiratory syncytial virus (RSV) in children at increased risk of severe disease. Since that time, the American Academy of Pediatrics has updated its guidance for the use of palivizumab 4 times as additional data became available to provide a better understanding of infants and young children at greatest risk of hospitalization attributable to RSV infection. The updated recommendations in this policy statement reflect new information regarding the seasonality of RSV circulation, palivizumab pharmacokinetics, the changing incidence of bronchiolitis hospitalizations, the effect of gestational age and other risk factors on RSV hospitalization rates, the mortality of children hospitalized with RSV infection, the effect of prophylaxis on wheezing, and palivizumab-resistant RSV isolates. This policy statement updates and replaces the recommendations found in the 2012 Red Book.

Since the last policy statement from the American Academy of Pediatrics (AAP) concerning meningococcal vaccine was published in 2011, 2 meningococcal conjugate vaccines have been licensed for use in infants (Hib-MenCY-TT and MenACWY-CRM). The Centers for Disease Control and Prevention (CDC) has published new recommendations, “Prevention and Control of Meningococcal Disease: Recommendations of the Advisory Committee on Immunization Practices,” which have been endorsed by the AAP. However, the CDC recommendations were published before licensure of MenACWY-CRM for infant use. This policy statement updates the AAP recommendations for use of meningococcal vaccines in children and adolescents. A more comprehensive review of background and technical information can be found in the CDC publication.

The resurgence of pertussis in the United States has stimulated considerable public health interest in developing new vaccination strategies to improve control of pertussis. The purpose of this article is to review the US Food and Drug Administration's regulatory framework for the prelicensure clinical evaluation of preventive vaccines and the clinical approaches that have been used to demonstrate effectiveness of US-licensed vaccines containing an acellular pertussis component.

The Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention and the American Academy of Pediatrics approved updated recommendations for the use of quadravalent (serogroups A, C, W-135, and Y) meningococcal conjugate vaccines (Menactra [Sanofi Pasteur, Swiftwater, PA] and Menveo [Novartis, Basel, Switzerland]) in adolescents and in people at persistent high risk of meningococcal disease. The recommendations supplement previous Advisory Committee on Immunization Practices and American Academy of Pediatrics recommendations for meningococcal vaccinations. Data were reviewed pertaining to immunogenicity in high-risk groups, bactericidal antibody persistence after immunization, current epidemiology of meningococcal disease, meningococcal conjugate vaccine effectiveness, and cost-effectiveness of different strategies for vaccination of adolescents. This review prompted the following recommendations: (1) adolescents should be routinely immunized at 11 through 12 years of age and given a booster dose at 16 years of age; (2) adolescents who received their first dose at age 13 through 15 years should receive a booster at age 16 through 18 years or up to 5 years after their first dose; (3) adolescents who receive their first dose of meningococcal conjugate vaccine at or after 16 years of age do not need a booster dose; (4) a 2-dose primary series should be administered 2 months apart for those who are at increased risk of invasive meningococcal disease because of persistent complement component (eg, C5–C9, properdin, factor H, or factor D) deficiency (9 months through 54 years of age) or functional or anatomic asplenia (2–54 years of age) and for adolescents with HIV infection; and (5) a booster dose should be given 3 years after the primary series if the primary 2-dose series was given from 2 through 6 years of age and every 5 years for persons whose 2-dose primary series or booster dose was given at 7 years of age or older who are at risk of invasive meningococcal disease because of persistent component (eg, C5–C9, properdin, factor H, or factor D) deficiency or functional or anatomic asplenia.

Palivizumab was licensed in June 1998 by the US Food and Drug Administration for prevention of serious lower respiratory tract disease caused by respiratory syncytial virus (RSV) in pediatric patients who are at increased risk of severe disease. Safety and efficacy have been established for infants born at or before 35 weeks' gestation with or without chronic lung disease of prematurity and for infants and children with hemodynamically significant heart disease. The American Academy of Pediatrics (AAP) published a policy statement on the use of palivizumab in November 1998 (American Academy of Pediatrics, Committee on Infectious Diseases and Committee on Fetus and Newborn. Pediatrics. 1998;102[5]:1211–1216) and revised it in December 2003 (American Academy of Pediatrics, Committee on Infectious Diseases and Committee on Fetus and Newborn. Pediatrics. 2003;112[6 pt 1]:1442–1446), and an AAP technical report on palivizumab was published in 2003 (Meissner HC, Long SS; American Academy of Pediatrics, Committee on Infectious Diseases and Committee on Fetus and Newborn. Pediatrics. 2003;112[6 pt 1]:1447–1452). On the basis of the availability of additional data regarding seasonality of RSV disease as well as the limitations in available data on risk factors for identifying children who are at increased risk of serious RSV lower respiratory tract disease, AAP recommendations for immunoprophylaxis have been updated in an effort to ensure optimal balance of benefit and cost from this expensive intervention. This statement updates and replaces the 2003 AAP statement and the 2006 Red Book and is consistent with the 2009 Red Book recommendations.

This policy statement contains provisional recommendations for use of the quadrivalent human papillomavirus vaccine in girls and women. A full policy statement from the American Academy of Pediatrics is forthcoming.

The purpose of this statement is to update recommendations for routine use of seasonal influenza vaccine and antiviral medications for the prevention and treatment of influenza in children. Highlights for the upcoming 2013–2014 season include (1) this year’s trivalent influenza vaccine contains an A/California/7/2009 (H1N1) pdm09-like virus (same as 2012–2013); an A/Texas/50/2012 (H3N2) virus (antigenically like the 2012–2013 strain); and a B/Massachusetts/2/2012-like virus (a B/Yamagata lineage like 2012–2013 but a different virus); (2) new quadrivalent influenza vaccines with an additional B virus (B/Brisbane/60/2008-like virus [B/Victoria lineage]) have been licensed by the US Food and Drug Administration; (3) annual universal influenza immunization is indicated with either a trivalent or quadrivalent vaccine (no preference); and (4) the dosing algorithm for administration of influenza vaccine to children 6 months through 8 years of age is unchanged from 2012–2013. As always, pediatricians, nurses, and all health care personnel should promote influenza vaccine use and infection control measures. In addition, pediatricians should promptly identify influenza infections to enable rapid antiviral treatment, when indicated, to reduce morbidity and mortality.

The purpose of this statement is to update recommendations for routine use of trivalent seasonal influenza vaccine and antiviral medications for the prevention and treatment of influenza in children. The key points for the upcoming 2012–2013 season are: (1) this year’s trivalent influenza vaccine contains A/California/7/2009 (H1N1)–like antigen (derived from influenza A [H1N1] pdm09 [pH1N1] virus); A/Victoria/361/2011 (H3N2)–like antigen; and B/Wisconsin/1/2010–like antigen (the influenza A [H3N2] and B antigens differ from those contained in the 2010–2011 and 2011–2012 seasonal vaccines); (2) annual universal influenza immunization is indicated; and (3) an updated dosing algorithm for administration of influenza vaccine to children 6 months through 8 years of age has been created. Pediatricians, nurses, and all health care personnel should promote influenza vaccine use and infection control measures. In addition, pediatricians should promptly identify influenza infections to enable rapid treatment, when indicated, to reduce morbidity and mortality.

Health care−associated infections in the NICU are a major clinical problem resulting in increased morbidity and mortality, prolonged length of hospital stays, and increased medical costs. Neonates are at high risk for health care−associated infections because of impaired host defense mechanisms, limited amounts of protective endogenous flora on skin and mucosal surfaces at time of birth, reduced barrier function of neonatal skin, the use of invasive procedures and devices, and frequent exposure to broad-spectrum antibiotics. This statement will review the epidemiology and diagnosis of health care−associated infections in newborn infants.

The purpose of this statement is to update current recommendations for routine use of trivalent seasonal influenza vaccine and antiviral medications for the prevention and treatment of influenza in children.

Drinking water for approximately one sixth of US households is obtained from private wells. These wells can become contaminated by pollutant chemicals or pathogenic organisms, leading to significant illness. Although the US Environmental Protection Agency and all states offer guidance for construction, maintenance, and testing of private wells, there is little regulation, and with few exceptions, well owners are responsible for their own wells. Children may also drink well water at child care or when traveling. Illness resulting from children's ingestion of contaminated water can be severe. This report reviews relevant aspects of groundwater and wells; describes the common chemical and microbiologic contaminants; gives an algorithm with recommendations for inspection, testing, and remediation for wells providing drinking water for children; reviews the definitions and uses of various bottled waters; provides current estimates of costs for well testing; and provides federal, national, state, and, where appropriate, tribal contacts for more information.

The American Academy of Pediatrics recommends annual influenza immunization for all children with high-risk conditions who are 6 months of age and older, for all healthy children ages 6 through 59 months, for all household contacts and out-of-home caregivers of children with high-risk conditions and of healthy children younger than 5 years, and for all health care professionals.To more fully protect against the morbidity and mortality of influenza, increased efforts are needed to identify and immunize all children at high risk and all healthy children ages 6 through 59 months and to inform their parents when annual immunizations are due. Previously unimmunized children who are at least 6 months of age but younger than 9 years should receive 2 doses of influenza vaccine, given 1 month apart, beginning as soon as possible on the basis of local availability during the influenza season. If children in this cohort received only 1 dose for the first time in the previous season, it is recommended that 2 doses be administered in the current season. This recommendation applies only to the influenza season that follows the first year that a child younger than 9 years receives influenza vaccine. A child who then also fails to receive 2 doses the next year should be given only 1 dose per year from that point on. Influenza vaccine should also continue to be offered throughout the influenza season, even after influenza activity has been documented in a community.On the basis of global surveillance of circulating virus strains, the influenza vaccine may change from year to year; indeed, 1 of the 3 strains in the 2007–2008 vaccine is different from the previous year's vaccine. All health care professionals, influenza campaign organizers, and public health agencies should develop plans for expanding outreach and infrastructure to immunize all children for whom influenza vaccine is recommended. Appropriate prioritization of administering influenza vaccine will also be necessary when vaccine supplies are delayed or limited. Because the influenza season often extends into March, immunization against influenza is recommended to continue through late winter and early spring. Lastly, it is recommended that for the 2007–2008 season, and likely beyond, health care professionals do not prescribe amantadine or rimantadine for influenza treatment or chemoprophylaxis, because widespread resistance to these antiviral medications now exists among influenza A viral strains. However, oseltamivir and zanamivir can be prescribed for treatment or chemoprophylaxis, because influenza A and B strains remain susceptible.

Since the American Academy of Pediatrics published a statement titled “Infection Control in Physicians' Offices” (Pediatrics. 2000;105[6]:1361–1369), there have been significant changes that prompted this updated statement. Infection prevention and control is an integral part of pediatric practice in ambulatory medical settings as well as in hospitals. Infection prevention and control practices should begin at the time the ambulatory visit is scheduled. All health care personnel should be educated regarding the routes of transmission and techniques used to prevent transmission of infectious agents. Policies for infection prevention and control should be written, readily available, updated annually, and enforced. The standard precautions for hospitalized patients from the Centers for Disease Control and Prevention, with a modification from the American Academy of Pediatrics exempting the use of gloves for routine diaper changes and wiping a well child's nose or tears, are appropriate for most patient encounters. As employers, pediatricians are required by the Occupational Safety and Health Administration to take precautions to identify and protect employees who are likely to be exposed to blood or other potentially infectious materials while on the job. Key principles of standard precautions include hand hygiene (ie, use of alcohol-based hand rub or hand-washing with soap [plain or antimicrobial] and water) before and after every patient contact; implementation of respiratory hygiene and cough-etiquette strategies for patients with suspected influenza or infection with another respiratory tract pathogen to the extent feasible; separation of infected, contagious children from uninfected children when feasible; safe handling and disposal of needles and other sharp medical devices and evaluation and implementation of needle-safety devices; appropriate use of personal protective equipment such as gloves, gowns, masks, and eye protection; and appropriate sterilization, disinfection, and antisepsis.

The mercury-based vaccine preservative thiomersal has come under scrutiny in recent months because of its presence in certain vaccines that provide the foundation of childhood immunisation schedules. Over the past decade new vaccines have been added to the recommended childhood schedule, and the relatively smaller bodyweight of infants has led to concern that the cumulative exposure of mercury from infant vaccines may exceed certain guidelines for the human consumption of mercury. In the US, government agencies and professional societies have recently recommended that thiomersal be removed altogether from vaccines. Some involved in developing vaccine policy feel that the evidence to support these safety concerns has not risen to the level required for such a response. This apparent divergence of opinion has left healthcare professionals and the public with uncertainty about the potential health effects from low level exposure to thiomersal as well as the necessity of removing thiomersal from vaccines. At present, scientific investigation has not found conclusive evidence of harm from thiomersal in vaccines. As a precautionary measure, efforts are under way to remove or replace thiomersal from vaccines and providers should anticipate the availability of more vaccine products that are thiomersal-free over the coming years.

ContextClinical trials evaluate a vaccine’s safety before approval, but some risks may escape detection or adequate characterization until larger population exposures occur after licensure.ObjectiveTo summarize reports of events occurring after vaccination with 7-valent pneumococcal conjugate vaccine (PCV), including those that may warrant further investigation to assess possible causation by PCV.DesignDescriptive epidemiology of reports submitted to the Vaccine Adverse Event Reporting System (VAERS), a national passive surveillance database.Setting and PatientsUnited States during first 2 years after licensure of PCV (February 2000 through February 2002). Reports studied were for children younger than 18 years and vaccinated with PCV.Main Outcome MeasuresNumbers and proportional distributions of reports.ResultsA total of 4154 reports of events following PCV were submitted to VAERS, for a rate of 13.2 reports per 100 000 doses distributed. Multiple vaccines were given in 74.3% of reports.The most frequently reported symptoms and signs included fever, injection site reactions, fussiness, rashes, and urticaria. Serious events were described in 14.6% of reports. There were 117 deaths, 23 reports of positive rechallenges, and 34 cases of invasive pneumococcal infections possibly representing vaccine failure. Immune-mediated events occurred in 31.3% of reports. All 14 patients with anaphylactic or anaphylactoid reactions survived. Thrombocytopenia developed in 14 patients and serum sickness in 6 others. Neurologic symptoms occurred in 38% of reports. Seizures described in 393 reports included 94 febrile seizures.ConclusionsThe majority of reports to VAERS in the first 2 years after licensure of PCV described generally minor adverse events previously identified in clinical trials. The proportion of reports portraying serious events was similar to that for other vaccines. Although there are important limitations in passive surveillance data, and caution in their interpretation is necessary, symptoms experienced by a few children more than once after successive PCV doses, including allergic reactions, prolonged or abnormal crying, fussiness, dyspnea, and gastrointestinal distress, warrant continued surveillance, as do reports of rare but potentially serious events, such as seizures, anaphylactic or anaphylactoid reactions, serum sickness, and thrombocytopenia.